Medial Pivot Designs Versus Conventional Bearing Types in Primary Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Medial pivot (MP) designs are growing in popularity. They provide increased sagittal plane stability and theoretically replicate some aspects of native joint kinematics, which may improve total knee arthroplasty outcomes. Methods: A systematic review was performed of randomized controlled trials (RCTs) that compared MP designs with cruciate-retaining, posterior-stabilized (PS), ultracongruent, or mobile-bearings in primary total knee arthroplasty, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome measures were all clinical function scores, patient-reported outcome measures, and range of motion. The secondary outcome was complications. Two authors independently selected studies, performed data extraction, and risk-of-bias assessment. Studies at high risk of bias were excluded from meta-analysis. Treatment effects were assessed using random-effects meta-analysis and quantified using pooled mean differences or incidence rate differences as appropriate. Results: Eight RCTs met inclusion criteria. Five compared MP with PS, two with ultracongruent, and one with cruciate-retaining and mobile-bearing. In total, 350 knees were randomized to MP and 375 to conventional bearings. One RCT was excluded from meta-analysis because of high risk of bias. Meta-analysis comparing MP with PS only was possible and found no differences at any time points for any outcome measure, including 2-year follow-up for Oxford Knee Score (MD = 0.35 favoring PS; 95% CI −0.49 to 1.20) and range of motion (MD = 1.58 favoring MP; 95% CI −0.76 to 11.92, P = 0.30) and 12 months for Western Ontario Arthritis Index (MD = 4.42 favoring MP; 95% CI −12.04 to 3.20, P = 0.09). Conclusions: There is no difference in clinical outcomes, with contemporary measurement tools, at any time points, between MP and PS. There are insufficient RCTs comparing MP with other bearings.

Conclusions: There is no difference in clinical outcomes, with contemporary measurement tools, at any time points, between MP and PS. There are insufficient RCTs comparing MP with other bearings. P rimary total knee arthroplasty (TKA) can be performed with various articular bearings. Each influences joint stability, function, and implant survivorship differently, through unique geometries and levels of conformity. Some bearings are fixed to the tibial baseplate: cruciate-retaining (CR), ultracongruent (UC), and posterior-stabilized (PS). Mobile bearings (MBs) are able to move relative to the tibial baseplate. More recently, medial pivot (MP) (or medial stabilized) designs have been developed to replicate some aspects of native knee joint kinematics. [1][2][3] There are theoretical kinematic advantages of MP designs. They feature a conforming medial compartment in the sagittal and frontal planes that creates a shallow, "ball and socket" joint. The lateral compartment articulation is less congruent, to permit femoral roll back here and not in the medial compartment in flexion. 4 The increased medial conformity provides increased sagittal stability and distributes load over a wider surface area. 5 The adoption of MP designs into practice has been rapid in some regions, comprising for example 9.8% of all TKA performed in Australia. 6 The incidence of use, complications, survivorship, and modes of failure specific to MP designs remain unclear, 7 with limited published data. 4 Previous systematic reviews and meta-analyses have compared MP designs with conventional bearings by including all study designs, irrespective of study quality or risk of bias, and pooling all bearing types together. [8][9][10] By including only randomized controlled trials (RCTs) that compare MP designs with specific bearings, better quality evidence is expected. This systematic review and meta-analysis asks (1) in patients receiving primary TKA, do the clinical and patient-reported outcomes and (2) the incidence of complications differ between TKA performed with MP designs and other bearings: CR, UC, PS, or MB?

Search Strategy
This systematic review was performed according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses and protocol registered with PROSPERO (ID:CRD42022300190). A literature search was performed in MEDLINE, EMBASE, PubMed, Web of Science, and Scopus databases using a combination of controlled vocabulary and keywords. The search strategy in MEDLINE (Ovid) : 1. (medial* and (pivot* or stabili* or rotat* or congruent or "ball-and-socket" or "ball-insocket")).mp. 2. (anteromedial portal or AMP or MRK or SAIPH or GMK or Evolution or Advance).mp. 3. 1 or 2 4. (knee and (replacement* or arthroplast* or TKA or prosthes* or surgery)).mp. 5. (random* control* trial* or random* clinical trial* or RCT*).mp. 6. 3 and 4 and 5 7. Limit 6 to English The search included studies published in English between January 1, 1986, and March 25, 2022. The search was conducted by two independent investigators (G.S. and W.H.) using the Covidence Systematic Review Software (2021; Veritas Health Innovation). Where there was disagreement over study inclusions, the investigators reviewed the study together until consensus was reached with a further investigator if required (K.V.). The search was supplemented with hand searching conference proceedings and publication reference lists, and experts in the field were contacted to ensure complete capture of the literature.

Inclusion and Exclusion Criteria
We included RCTs of primary TKA that compared MP designs specifically with CR, UC, PS, or MB and that reported clinical outcomes and patient-reported outcome measures (PROMs) in adult patients aged 18 years and older. 11 Comparative studies that were not RCT designs, studies that included TKAs performed in patients aged younger than 18 years, studies that included revision TKA, and studies that only compared kinematic assessment of the knee or gait analysis were excluded.

Data Extraction
Data were extracted by the same two investigators (G.S. and W.H.) into an Excel (2003; Microsoft) spreadsheet, including study methods, participants, interventions, surgical technique, and outcomes. Where data were inadequate or not reported, attempts were made to contact the corresponding authors. The primary outcome measures included all clinical function scores, PROMs, and knee range of motion (ROM). Outcome measures related to kinematic assessment of the knee and gait analysis were not included. The secondary outcome measure was complications, specifically stiffness and aseptic revision. All extracted outcome variables were continuous and the mean differences were used as comparison. The data collected were analyzed using R version 3.6.3 (R Foundation for Statistical Computing) by a single investigator (T.S.).

Assessment of Risk of Bias
Two review investigators (G.S. and W.H.) independently assessed the risk of bias of the included studies using the Cochrane Risk-of-Bias tool for randomized trials. 12 Studies with a high risk of bias were excluded from the meta-analysis. No attempt was made to mask the trial reports. Where disagreement existed concerning the assessment, we reached consensus through discussion among all review authors.

Unit of Analysis Issues
The studies and data included in the final analysis were assessed for potential unit of analysis issues relating to the clustering of patients to the MP intervention or comparator group based on the surgeon or hospital and/or treated with bilateral TKA that were analyzed on a per surgical fixation basis. We expected heterogeneity in follow-up times and planned for pooled analysis of clinical outcomes and PROMs at short and medium intervals after the intervention. Complications were reported at the final follow-up of each study. Not all time points had sufficient data across all outcomes to run a meta-analysis, and only those outcomes and time points for which minimum data were available had meta-analysis performed. Where data were inadequately

Figure 1
Image showing study flow chart per PRISMA standards. Overall records identified 687 studies with final inclusion of five studies for quantitative analysis. PRISMA = preferred reporting items for systematic reviews and meta-analyses

Assessment of Heterogeneity
Heterogeneity (variation in the outcomes between studies) was assessed visually by inspection of forest plots and statistically using x 2 and I 2 tests. 13 A P value of ,0.1 for x 2 was set to indicate significant heterogeneity. I 2 was interpreted as 0% to 40% might not be important; 30% to 60% may represent moderate heterogeneity; 50% to 90% may represent substantial heterogeneity; 75% to 100% indicated considerable heterogeneity. 14

Data Synthesis
Outcome variables that were reported in a comparable manner among studies (criteria set a priori) were included in the meta-analysis. MP designs were compared separately against each bearing type: CR, UC, PS, and MB. Continuous outcomes were compared using a random-effects mean difference meta-analysis regression. A random-effects model was preferred over a fixedeffects approach to control for differences in the treatment effect between studies attributable to differences in study patient populations, settings, and surgeons. Continuous variables were reported as mean 6 SD, with the mean weighted for sample size. For all comparisons, P , 0.05 was considered significant. All analyses were conducted using R version 3.6.3 (R Foundation for Statistical Computing).

Systematic Review
The search strategy yielded 718 studies with 299 duplicates removed, leaving 419 titles and abstracts for screening. Three hundred eighty studies were deemed irrelevant leaving 20 studies to be assessed for eligibility. Agreement was obtained on eight studies for final inclusion after full-text review ( Figure 1). Seven studies were single (assessor) blinded RCTs, and one study was a single (assessor) blinded, three group parallel RCT (Table 1). Five studies compared MP with PS bearings, two with UC, and one with CR and MB. In total, 350 knees were randomized to MP and 375 to conventional bearings (194 PS, 99 MB, 55 UC, and 27 CR) ( Table 1). The risk of bias assessment showed overall some concern for risk of bias in five studies and high risk of bias in one study, which was excluded from meta-analysis (Table 2). For the studies with some concern for risk of bias, most issues were due to the randomization process and missing outcomes. Patient characteristics for the studies included are shown in Table 3. The raw data for the primary outcome measures are presented in Tables 4 to 6 and for the  secondary outcome measures in Table 7.   (Figure 2). The interaction test for subgroup difference did not suggest that the relationship was likely to be important (x 2 = 0.45, P = 0.80).  (Figure 3). The interaction test for subgroup difference did not suggest that the relationship was likely to be important (x 2 = 0.04, P = 0.85).

Range of motion
There was no notable difference in ROM between MP and PS bearings at any time point. Three studies compared preoperative ROM for 137 MP and 138 PS Low Low Some concern WH Low Low Some concern Low Low Some concern Dowsey et al. 17 JOA 2020 GS Some concern Low Low Low Low Some concern WH Some concern Low Low Low Low Some concern Edelstein et al. 18 J knee surg 2020 GS Some concern Low Some concern Low Some concern Some concern WH Some concern Low Some concern Low Some concern Some concern Ishida et al. 19 KSSTA 2014 GS Some concern Low Low Low Low Some concern WH Some concern Low Low Low Low Some concern Kim et al. 20 CORR 2009 GS Low Some concern Low Low Some concern WH Low Low Some concern Low Low Some concern Kulshrestha et al. 21 (Figure 6).

Discussion
The difference in clinical outcomes, PROMs, and complications for primary TKA performed with MP designs compared with conventional bearings is not known, and there is increased use of MP designs. This systematic review and meta-analysis of RCTs concluded that, to date, no differences have been documented in the shortterm clinical outcomes, PROMs, or complications between MP and PS bearings in TKA, with conventional measurement instruments, at any time point after surgery. Additional RCTs will be required to confirm or refute these findings. There are insufficient RCTs that compare MP designs with other bearings: CR, UC, or MB. Accordingly, the differences between MP designs and these bearings have not been determined.
To our knowledge, this is the first systematic review of RCTs that compared MP designs with conventional bearings, although meta-analysis was limited to comparison with PS bearings. Other systematic reviews and meta-analyses are limited by pooling of all study designs (retrospective and prospective), inclusion of study designs with a high risk-of-bias, pooling of all conventional bearing types into one group, and heterogeneity of included patients, 8-10 such as RCTs including both primary and revision procedures. 23 Notwithstanding, those reviews support our findings of no clear difference in clinical outcomes between MP and PS bearings. [8][9][10] The number of outcome measures that could be included in the meta-analysis was limited by inconsistency of outcome measures between studies, variation in the time of outcome measure reporting, and other study limitations with the reporting of results. Standardization of data reporting would improve the RCTs conducted and the ability to perform meta-analysis. 24 Metaanalysis was accordingly limited to three clinical outcome measures and PROMs. Although validated and widely used, the relatively crude outcome measures included in our meta-analysis evaluate general function of a TKA. It is possible that differences may exist  between MP and other TKA designs when alternate outcome measures are used, including those with lower ceiling effects or more demanding performance tests, which might identify small but notable differences between arthroplasty designs. Some of the hypothesized kinematic improvements of MP designs have been realized in gait analysis, but postoperative kinematics for MP (and CR and PS) bearings still do not match a native, nonarthritic joint 3 nor is benefit always seen. 25 Along with the hypothetical benefits, there are hypothetical disadvantages too. The increased conformity may lead to component impingement, which may limit femoral roll back and flexion in some patients. 26 Kinematic conflict can result when the articular geometry does not match the soft-tissue kinematics. 27 Retaining the PCL for example with the increased MP conformity can cause this, and two included studies recessed or selectively sacrificed the PCL. 20,21 Differences in surgical techniques may influence outcomes.
The successful TKA achieves both good clinical function and implant durability. The equivocal clinical results of MP designs when compared with PS bearings may support MP uptake. PS bearings have been the most common bearing in the United States, 28 where their use is currently declining, as in other countries. 6,29,30 One explanation for the decline of PS bearings is the increased long-term risk of revision with PS compared with CR bearings. 6,31 However, MP and PS bearings may have the same long-term revision risk, with CR bearings having a lower long-term risk. 6,7 This makes future RCTs comparing MP and CR bearings     CR bearings are the most common type of bearing used in primary TKA in Australia, 6 New Zealand, 29 the United Kingdom 30 and now in the United States. 28 The current difference in long-term revision rates of MP designs may change with follow-up of newer MP designs. None of the newest designs have greater than five years documented follow-up. 6 Long-term follow-up might be influenced by polyethylene quality, independent of the bearing design. No MP design reported in the Australian Registry is manufactured with highly crosslinked polyethylene (XLPE), a material known to decrease component loosening and revisions. 6,32 How the increased conformity of MP designs affect polyethylene wear is unknown. There are also variations in survivorship between individual MP designs, 7,33 which makes grouping MP designs vexed. An early MP design, for example, ADVANCE (MicroPort, Shanghai, China), experienced high revision rates and is excluded from comparisons in the Australian Registry. 6 There are also   concerns for the durability of some modern MP designs. Roentgen stereophotogrammetric analysis of the GMK Sphere (Medacta, Castel San Pietro, Switzerland) found comparatively high early tibial tray motion, usually associated with aseptic loosening. 34 There are limitations to this study. First, there are few RCTs which directly compare MP designs with conventional bearings. Other limitations relate to the inclusion and exclusion criteria of the included studies. Of the studies included in the systematic review, three solely included bilateral single-stage TKA, 15,20,21 and one study included both unilateral and bilateral TKA. 22 Two of these studies were included in the meta-analysis, 15,21 and it is unclear whether these patient populations represent patients in general. Furthermore, both the studies that included bilateral single-stage TKA recruited patients from India where the severity of arthritis, patient expectations, and postoperative rehabilitation may be distinct. Batra et al. 15 from India studied only Grade 4 Kellgren-Lawrence arthritic changes. Dowsey et al 17 (by comparison, working in Australia) included patients with Grade 2 to 4 changes. Other studies failed to quantify the preoperative status of patients. Batra et al 15 were alone in including patients with rheumatoid arthritis (13% of cases). Limitations and generalizability also relate to preoperative limb alignment. Two studies restricted inclusion to preoperative varus alignment and excluded valgus 19,22 while another excluded valgus .10°. 18 Of note, all studies but two 15,21 reported a goal of neutral (mechanical) alignment, despite recent interest in alternative TKA alignments.

Conclusions
This systematic review and meta-analysis of RCTs provide evidence that there are no, as yet identifiable, shortterm differences between MP and PS bearings for clinical outcomes, PROMs, or complications in primary TKA, at any time point. There are insufficient RCTs to compare Forest plot comparing risk of aseptic revision in MP designs and PS bearings. MP = medial pivot, PS = posterior-stabilized MP with other conventional bearings, and the clinical differences are unexplored and unknown. Additional RCTs will be required that use consistent outcome measures, including those with lower ceiling effects, with standardization of data reporting to define advantages of one TKA design over another. Continued monitoring of revision rates by registries is mandatory.